Hydrogel compositions

• US 9,861,701 B2
• Filed: 01/31/2017
• Issued: 01/09/2018
• Est. Priority Date: 11/09/2009
• Status: Active Grant

• Current Assignee: Spotlight Technology Partners LLC
• Original Assignee: Spotlight Technology Partners LLC
• Inventors: Sershen, Scott Robert, Pai, Suresh Subraya, Gong, Glen
• Primary Examiner(s): DICKINSON, PAUL W
• Application Number:
  US15/421,203
• Publication Number:
  US 20170274082A1
• Time in Patent Office: 343 Days
• CPC Class Codes: A61K 31/225 Polycarboxylic acids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/7036 having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
• CPC Class Codes: A61K 31/722 Chitin, chitosan
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 24/08 Polysaccharides A61L24/043 takes precedence
• CPC Class Codes: A61L 26/0023 Polysaccharides
• CPC Class Codes: A61L 26/008 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/042 Polysaccharides
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: C08J 2371/02 : Polyalkylene oxides
• CPC Class Codes: C08J 2405/08 : Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08J 3/075 : Macromolecular gels
• CPC Class Codes: C08J 3/12 : Powdering or granulating
• CPC Class Codes: C08K 5/06 : Ethers; Acetals; Ketals; Ortho-esters
• CPC Class Codes: C09D 105/08 : Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

Fragmented polysaccharide based hydrogel compositions and methods of making and using the same are provided. The subject polysaccharide based hydrogel compositions are prepared by combining a polysaccharide component with a hydrophilic polymer and a cross-linking agent. Also provided are kits and systems for use in preparing the subject compositions.

Claims

1. A composition comprising a plurality of hydrogel fragments, wherein each hydrogel fragment in the composition comprises:

a biologically active agent; and

a hydrogel comprising an acetylated polysaccharide, a multifunctional, multi-armed polyethylene glycol polymer and a multifunctional, multi-armed crosslinker of polyethylene glycol, wherein;

the acetylated polysaccharide or derivative thereof has a molecular weight of 1000 Dalton to 80,300 Dalton, a degree of deacetylation of 70% to 99%, and at least two nucleophilic groups and is directly covalently bonded to the multifunctional, multi-armed polyethylene glycol polymer and directly covalently bonded to the multifunctional, multi-armed crosslinker of polyethylene glycol;

the multifunctional, multi-armed polyethylene glycol polymer has a molecular weight of 5,000 Dalton to 30,000 Dalton, and comprises at least two nucleophilic groups and is directly covalently bonded to the acetylated polysaccharide or derivative thereof and is directly covalently bonded to the multifunctional, multi-armed crosslinker of polyethylene glycol; and

the multifunctional, multi-armed crosslinker of polyethylene glycol has a molecular weight of 5,000 Dalton to 30,000 Dalton, and comprises at least two electrophilic groups and is directly covalently bonded to the acetylated polysaccharide or derivative thereof and is directly covalently bonded to the multifunctional, multi-armed polyethylene glycol polymer,

wherein the acetylated polysaccharide or derivative thereof does not act as a cross-linking agent in the hydrogel.

2. The composition of claim 1, wherein the hydrogel fragments are a dry powder.

3. The composition of claim 1, wherein the hydrogel fragments are lyophilized.

4. The composition of claim 1, wherein the hydrogel fragments are milled fragments.

5. The composition of claim 1, wherein the hydrogel fragments are pulverized fragments.

6. The composition of claim 1, wherein the hydrogel fragments are crushed fragments.

7. The composition of claim 1, wherein the hydrogel fragments are grinded fragments.

8. The composition of claim 1, wherein the biologically active agent is a steroid.

9. The composition of claim 8, wherein the steroid is mometasone furoate or triamcinolone.

10. The composition of claim 1, wherein the biologically active agent is an antibiotic.

11. The composition of claim 10, wherein the antibiotic is gentamicin.

12. The composition of claim 1, wherein the biologically active agent is a plasma protein, an enzyme, an antiseptic agent, an antineoplastic agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, a growth factor, an anesthetic, a cell suspension, a cytotoxin, a cell proliferation inhibitor, a biomimetic, an analgesic, a chemotherapeutic, a vasoconstrictor, a vasodilator, a cholesterol-lowering agent, a procoagulant, a selective serotonin reuptake inhibitor, a bone morphogenic protein, a growth factor, or a growth factor analog.

13. The composition of claim 1, wherein the polysaccharide or derivative thereof is a chitin, chitosan, or derivative thereof.

14. The composition of claim 1, wherein the polysaccharide or derivative thereof is soluble in an aqueous solution.

15. The composition of claim 14, wherein the aqueous solution is alkaline and the polysaccharide or derivative thereof is soluble in the aqueous solution up to a concentration of 30 mM.

16. The composition of claim 1, further comprising one or more of a thickening agent, a foaming agent, a visualization agent, or a radiopaque agent.

17. The composition of claim 1, wherein the multifunctional, multi-armed polyethylene glycol polymer comprises ester groups to provide for degradation via hydrolysis.

18. The composition of claim 1, wherein the ratio of multifunctional, multi-armed polyethylene glycol polymer to polysaccharide or derivative thereof is from 5:

1 to 10;

1 by mass.

19. A kit, comprising:

the composition comprising the plurality of hydrogel fragments of claim 1, and

a delivery device to provide for delivery of the hydrogel fragments to a target area or tissue.

20. The kit of claim 19, wherein the composition comprising the plurality of hydrogel fragments is provided in a first container and a buffer solution is provided in a second container.

21. The kit of claim 20, wherein the container for the composition comprising the plurality of hydrogel fragments comprises a first syringe and the container for the buffer solution comprises a second syringe.

22. The kit of claim 20, wherein the container for the composition comprising the plurality of hydrogel fragments comprises a pouch and the container for the buffer solution comprises a syringe.

23. The kit of claim 20, wherein the composition comprising the plurality of hydrogel fragments and a buffer solution are provided within a single syringe.

24. The kit of claim 23, wherein the syringe is a dual chamber syringe, and wherein the composition comprising the plurality of hydrogel fragments is provided in a first chamber of the syringe and the buffer solution is provided in a second chamber of the syringe.

25. The kit of claim 19, wherein the composition comprising the plurality of hydrogel fragments is provided as a dry particulate in a container.

26. The kit of claim 19, wherein the composition comprising the plurality of hydrogel fragments is provided as a semi- or fully hydrated particulate in a container.